Mutation analysis of SLC7A9 in cystinuria patients in Sweden

Cystinuria is an autosomal recessive disorder characterized by increased urinary excretion of cystine and dibasic amino acids, which cause recurrent stone formation in affected individuals. Three subtypes of cystinuria have been described (type I, II, and III): type I is caused by mutations in the SLC3A1 gene, whereas nontype I (II and III) has been associated with SLC7A9 mutations. Of the 53 patients reported in our previous work, patients that showed SLC7A9 mutations in single-strand conformation polymorphism (SSCP) screening and/or either lacked or showed heterozygosity for SLC3A1 mutations were included in the present study. The entire coding region and the exon/intron boundaries of the SLC7A9 gene were analyzed by means of both SSCP and DNA sequencing in 16 patients, all but one of which were clinically diagnosed as homozygous cystinurics. Three novel SLC7A9 mutations were identified in the patient group: two missense mutations (P261L and V330M), and one single base-pair deletion (1009 delA). We also detected the previously reported A182T and nine novel polymorphisms in the patients. Mutations V330M and 1009delA occurred on different alleles in one individual, and we suggest that these mutations cause cystinuria in this patient. One patient that was homozygously mutated in the SLC3A1 gene carried the third novel mutation (P261L). We conclude that SLC3A1 is still the major disease gene among Swedish cystinuria patients, with only a minor contribution of SLC7A9 mutations as the genetic basis of cystinuria. The absence of SLC3A1 and SLC7A9 mutations in a substantial proportion of the patients implies that mutations in parts of the genes that were not analyzed may be present, as well as large deletions that escape detection by the methods used. However, our results raise the question of whether other, as yet unknown genes, may also be involved in cystinuria

Incidence of and risk factors for nephrolithiasis in patients with gout and the general population, a cohort study

Abstract Background Nephrolithiasis (NL) is known to be associated with gout, although there are few comparative studies on risk and risk factors for NL in gout compared to population cohorts. In this cohort study we investigated: (1) overall incidence of NL in gout (cases) and general population controls; (2) risk and risk factors (common comorbidities and medications) for first-time NL in cases and controls separately. Methods Cases (n = 29,968) and age-matched and sex-matched controls (n = 138,678) were identified from the regional healthcare database in western Sweden (VEGA). The analyzed risk factors (comorbidities and current medication use) for first-time NL, and socioeconomic factors were retrieved from VEGA and other national Swedish registers. For cases, follow up began on 1 January 2006 or on the first diagnosis of gout if this occurred later, and for controls on their index patient’s first diagnosis of gout. Follow up ended on death, emigration or 31 December 2012. Incidence rates (IR) per 1000 person-years and hazard ratios (HR) were calculated. The incidence calculations were performed for cases (regardless of prior NL) and their controls. HRs with first occurrence of NL as outcome were calculated only in those without previous NL. Results In cases there were 678 NL events (IR: 6.16 events per 1000 person-years (95% CI: 5.70–6.64) and in controls 2125 NL events (IR 3.85 events per 1000 person-years (95% CI: 3.69–4.02), resulting in an age-sex-adjusted incidence rate ratio of 1.60 (95% CI:1.47–1.74). Point estimates for predictive factors were similar in cases and controls, except for a significant interaction for losartan which increased the risk of NL only in controls (HR = 1.49 (95% CI: 1.03–2.14). Loop diuretics significantly decreased the risk of NL by 30–34% in both cases and controls. Further significant predictors of NL in gout cases were male sex, diabetes and obesity and in controls male sex and kidney disease. Conclusions The risk (age and sex adjusted) of NL was increased by 60% in cases compared to controls. None of the commonly used medications increased the risk of NL in gout patients

Additional file 1: Tables S1-S6. of Incidence of and risk factors for nephrolithiasis in patients with gout and the general population, a cohort study

and supplementary Figures S1-S2. Table S1 Definitions of comorbidities by ICD-10-codes given at a visit to physician, based on data in the National Patient Register and dispensed medication in the national Prescribed Drugs Register (ever before start of follow up). Table S2. Definitions of co-medications by the Anatomical Therapeutic Chemical (ATC) Classification System for dispensed medication in the national Prescribed Drugs Register. Table S3. Description of regional and national registers used in the study. Table S4. Incidence rates of NL in cases/controls without prior NL. Table S5. Comorbidities and medications at baseline for cases and controls without prior NL, stratified by sex. Table S6. Age-adjusted and sex adjusted hazard ratios for first-time NL in cases and controls separately, with exposure defined as having at least one batch of the medication dispensed before start of follow up and at least an additional batch of the medication dispensed during follow up. Non-exposure was defined as having no medication dispensed before follow up and no medication dispensed during follow up. Figure S1. Forest plot with hazard ratios for first-time NL in men, in cases with gout and controls separately. Figure S2. Forest plot with hazard ratios for first-time NL in women, in cases with gout and controls separately. (DOC 1465 kb

Behavioral momentum in the treatment of noncompliance.

Behavioral momentum refers to the tendency for behavior to persist following a change in environmental conditions. The greater the rate of reinforcement, the greater the behavioral momentum. The intervention for noncompliance consisted of issuing a sequence of commands with which the subject was very likely to comply (i.e., high-probability commands) immediately prior to issuing a low-probability command. In each of five experiments, the high-probability command sequence resulted in a "momentum" of compliant responding that persisted when a low-probability request was issued. Results showed the antecedent high-probability command sequence increased compliance and decreased compliance latency and task duration. "Momentum-like" effects were shown to be distinct from experimenter attention and to depend on the contiguity between the high-probability command sequence and the low-probability command